基因富集及meta分析筛选非小细胞肺癌发生发展关键基因的研究

Screening Key Genes Associated with the Development and Progression of Non- small Cell Lung Cancer Based on Gene-enrichment Analysis and Meta-analysis

背景与目的非小细胞肺癌(non-small cell lung cancer,NSCLC)是全球最常见的恶性肿瘤之一,其发病遗传机制仍不清楚。本研究旨在筛选影响NSCLC发生发展的关键基因和通路,为NSCLC发病遗传机制及靶向治疗的研究奠定科学基础。方法运用基因组富集分析(gene set enrichment analysis,GSEA)以及对单套数据集单个基因元分析(meta-analysis,meta)的方法,筛选出在转录水平上影响NSCLC发生发展的关键通路和基因。结果通过GSEA和meta两种分析方法得出的通路中,重叠性较高的主要为粘着斑通路和细胞骨架肌动蛋白调控通路。在粘着斑通路中31个基因具有统计学意义(P<0.05);细胞骨架肌动蛋白调控通路中32个基因具有统计学意义(P<0.05)。结论粘着斑通路和细胞骨架肌动蛋白调控通路可能与NSCLC的发生发展有重要的联系,后续本研究小组将对这两条通路中的具有统计学意义的基因进行生物功能学上的验证。

Background and objective Non-small cell lung cancer （NSCLC） is one of the most common malignant tumors; however, its causes are still not completely understood. This study was designed to screen the key genes and pathways re^ated to NSCLC occurrence and development and to establish the scientific foundation for the genetic mechanisms and tar- geted therapy of NSCLC. Methods Both gene set-enrichment analysis （GSEA） and meta-analysis （meta） were used to screen the critical pathways and genes that might be corretacted with the development and progression of lung cancer at the transcription level. Results Using the GSEA and meta methods, focal adhesion and regulation of actin cytoskeleton were determined to be the more prominent overlapping significant pathways. In the focal adhesion pathway, 31 genes were statistically significant （P〈0.05）, whereas in the regulation ofactin cytoskeleton pathway, 32 genes were statistically significant （P〈0.05）. Conclusion The focal adhesion and the regulation of actin cytoskeleton pathways might play important roles in the occurrence and development of NSCLC. Further studies are needed to determine the biological function for the positiue genes.